title: [Brain development and glutamate].
abstract: The involvement of glutamate in early brain development has been somewhat controversial. A large body of in vitro evidences indicates that the neurotransmitter glutamate influences early developmental events such as proliferation, migration, and differentiation. Paradoxically, loss-of-function mouse models of glutamatergic signaling that are generated by genetic deletion of receptors or the process of glutamate release exhibit normal brain development. The absence of an effect following genetic disruption of glutamatergic signaling might reflect compensation from other neurotransmitters such as GABA and glycine, both of which can depolarize immature neurons similar to glutamate. To overcome this potential confusion, we examined the direct consequences of extracellular glutamate buildup on brain development by reducing the levels of glutamate transporters GLAST and GLT1. GLAST/GLT1 double knockout mice (DKO) exhibit multiple brain defects, including cortical, hippocampal, and amygdalar disorganization with perinatal mortality. Several essential aspects of neuronal development, such as stem cell proliferation, radial migration, and neuronal differentiation were impaired in these mutants. The deletion of N-methyl-D-aspartate (NMDA) receptor 1 subunit in DKO mice almost completely rescued multiple brain defects. These results provide direct in vivo evidence that glutamatergic activity through NMDA receptors does indeed modulate early brain developmental processes.
authors.affiliation: Laboratory of Molecular Neuroscience, Medical Research Institute, Tokyo Medical and Dental University.
authors.forename: Kohichi
authors.initials: K
authors.lastname: Tanaka
mesh_terms: D027322:Amino Acid Transport System X-AG / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000254:growth & development* / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D009474:Neurons / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000235:genetics / Q000378:metabolism; D009435:Synaptic Transmission
chemical_list: D027322:Amino Acid Transport System X-AG; D018377:Neurotransmitter Agents; D018698:Glutamic Acid